Steroid aldehydes and process



United States Patent *0 STEROID ALDEHYDES AND PROCESS Robert B.Woodward, Belmont, Mass., assignor to Research Corporation, New York, N.Y., a corporation of New York No Drawing. Application January 31, 1952,Serial No. 269,330

5 Claims. (Cl. 260-3973) L i cmofi i) CH|O i ii (I) OH (H) (VIII).

1 3:0 on J o 2,701,807 Patente Feb. s, 1955 2 The cis-adduct (M. P.93-95 11) obtainedby the Diels-Alder condensation of 1,3-butadiene andZ-methyl- S-methoxy-benzoquinone is converted to the trans-adduct, trans.t-2-rnethoxy-9-methyl-5,8,9,l0=tetrahydro -l,4-naphth'oqu'inonex fl) bydissolving in an aqueous alkaline organic solvent and acidifyingafteriseedingswith the transisomer. t

'The trans-adduct is reduced to the corresponding glycol (II) withlithium aluminum hydride, and the glycol is converted to the ketol,1-hydroxy-2-keto-9-methyl-1,2,5,- 8,9,10-hexahydronaphthalene (III), -bytreatment with a dilute: mineral acid. The, ketolH-is' then esterified(IV) with any organic carboxylic acid, for example, acetic acid.

The ketol ester (IV) is reducedby treatment with zinc 'inaceticanhydride or 'in an inertorgafiicnisdlvent to2-k'eto-9-methyl-1,2,5,8,9,lo-hexahydronaphthalene v (V). The bicyclicketone (V) is formylated at position. ,1 r to give thel-hydr'oxymethylene derivative (VI .-which is condensed withethylvinylketone to give l-aldehyde-l-(flbutyroethyl) 2 keto9-methyl-1,2,5,8,9,lo-hexahydronaphthalene (VII).

Treatment of compound (VII) with mild condensing agents such aspotassium hydroxide-in an aqueous organic solvent or hydrogen chloridein aceticracid converts it to the tricycli'cketone,1;14-dimethyl-2-ket0-2,3,4,5,8,-

H (In) (XVII) CHO L CHr-CHO t l (xvm (XIXb)12,13,l4-octahydrophenanthrene (VIII), which has the desired anti-transconfiguration.

The tricyclic ketone (VIII) is oxidized to the 6,7- glycol (IX).Oxidation with osmium tetroxide typically gives the two cis-isomers bothof which are usable in the succeeding steps of the method. Otheroxidizing agents may give the trans-isomers, which may also be used inthe succeeding steps. Perbenzoic acid gives the 6,7-oxide whichhydrolyzes to the trans-glycols. Silver benzoate and iodine gives thedibenzoate of the glycol. Hydrogen peroxide may also be used as theoxidizing agent, for example, with osmium tetroxide as catalyst.

The hydroxyl groups of the glycol (IX) are protected by reaction with aketone, such as acetone (X), and protected compound hydrogenated at the9,10-double bond, for example, with hydrogen at atmospheric pressure ina non-polar solvent, such as dry benzene, in the presence of ahydrogenating catalyst, to, produce the dihydro derivative (XI), whichis formylated at position 3 (XII). The formyl group of compound (XII) isprotected by reacting it with a secondary amine, such as methylaniline,to give the methylanilino derivative (XIII).

Compound XII is reacted with acrylonitrile in the presence of aquaternary nitrogen base to give the isomeric cyanoethyl compounds XIVaand XIVb, which are preferably not separated at this stage but arehydrolyzed to the corresponding carboxyethyl compounds. The keto acidsmay be separated by taking them up in ether. A

" the presence of a small amount of sodium acetate.

keto acid (XVa) melting at C. (labile) and C. (stable) crystallizes fromthe ether and the other isomeric keto acid (XVb) is obtained as an oilby evaporation of the ether. The oily acid has the desired configurationat asymmetric carbon atom 1.

The keto acid (XVb) is converted to the enol lactone (XVI), for example,by boiling with acetic anhydride fin T e lactone (XVI) is now convertedto the tetracyclic ketone (XVII), having a D-homosteroid ring structureby condensing with a methyl magnesium halide, decomposing the additionproduct with acid and treating the product thus obtained with diluteaqueous alkali in a water-miscible organic solvent.

The homo-D-ring of ketone (XVII) may now be converted to a cyclopentanoring by opening and reclosing the ring, for example, by the followingsteps: The ketone (XVII) is oxidized, for example, with H104, to thedialdehyde (XVIII), l,2-bis(aldehydomethyl)-2,IS-dimethyl- 7 ketol,2,3,5,6,7,9,l0,11,l3 decahydrophenanthrene, and the dialdehyde iscondensed to the l7-aldehyde steroid, A9,(l1),l6 bisdehydro 21norprogesterone (XIX) by heating a solution of the dialdehyde in anorganic solvent. Some of the isomeric l5-aldehyde (XIXa) is also formed.The aldehydes XIX and XlXa have the same steric configuration at theasymmetric carbon atoms as the natural steroid hormones of the adrenalcortex such as .cortisoneand maybe converted .into .these hormonesiby.already available .procedures'.

"Ihe .following specific examples are illustrative of the .methodsandcompounds of the invention:

Isomerization of the cis-adduct to the trans-adduct Sixtygrams of the.cis-addust (M. P. 93-95" C.) ob- .tainedlby the Dials-Aldercondensation of 1,3-butad1ene and .2-methyl-5 methoxybenzoquinone,purified by recrystallization and almost colorless, is dissolved in 180ml. of dioxane. Solution :is facilitated by warming to 40'-50 C. .Fiveper cent more than the calculated amountgof about 1N sodiumihydroxidesolution (3.12 ml., '.0;975.N) is addedover min. with stirringin anatmosphere of nitrogen. A brownish orange solution contaming-aboutlguof. suspended solid is obtained. ThlS solution is diluted by theaddition of 600 ml. of water and then seeded with 3 g. .of finelypowdered trans-.adduct P. 125-127" -C.). At. this point it is essentialto ascertain that most of theseed has remained undissolved. If there beexcess alkali present, .the seed material will .ofcourse go intosolution; in that case moretrans-adduct should be added till there is anappreciable amountof undissolved solid in suspension. About 1Nhydrochloric acid is added dropwise to the seeded solution'withvigorous-stirring; a solid startsto separate immediately. Additionwofacid is stopped when the solution changes color to lemon yellowindicating complete neutralization (pH 5.) of the base. Some more water(200.ml.) is added and the solid product is collected by filtration,washed four times with water and dried. A.finely granular, lighttancolored solid, M. P. 126-129" C., is obtained. ThlS material .is pureenough for use in the.next;step without further purification.

Glycol ('1l).The trans-adduct '(I) (130 g.) in dry pure redistilledvtetrahydrofuran (1 1.) is slowly added to a stirred solution of lithiumaluminum hydride (24g) in.dr y ether (1.4 l.) in an atmosphere ofnitrogen. The addition iscontrolled so as tokeep the mixture reflux nggently (addition time ca. 2 /2 hrs.). During the addition a viscoussticky complex separates onto the stirrer, making stirringdifficult.Thecomplex towards the end of the addition becomes more .granular, andat the end a suspension of a white powder isobtained. Stirring iscontinued for a further /2 hour, and ethyl acetate is then slowly addedto the ice-cooled stirredsuspension until no. more reaction is observed(the reaction .is very .exothermic and the ethyl acetate must be addedvery carell Pffter the excess LiAlHthas been..decomposed by-theadditiorrof ethyl acetate, a saturated solution of NazSQ-a. 'isaddeddropwise, with stirring, to the reaction mixture. The whitesuspension soon becomes light yellow. During the entire addition .ofsaturated sodiumsulphate solution, rapid stirring is continued so thatthe LiAlH4 complex clinging to the sides of the flaskv may be washeddown. Addition of ;the saturated solutionis continued until theprecipitate becomes slightly wet (atwhich time it starts clinging to thesides of the flask). Without stopping the stirring about 200 ,gms. MgSO4;(anhyd.) are added. Rapid stirring is continued foranother 10 minutes.The precipitate is then filtered from the ethereal solution and washedthoroughly with excess ethyl ether. The filtrate and washingsareconcentrated, last traces of solvent removed at the water pump, and theviscous oil obtained is diluted with a small amount of ethyl ether andallowed to crystallize in the refrigerator overnight. The crude glycolmelts at about 128l33 C.

Ketol (III-).-The crude glycol (68 g.) is dissolved in reagent gradedioxan (375 cc.) and 2 N sulfuric acid (300 cc.) is added. The solutionis allowed to stand for 24 hours at room temperature and is then pouredinto ether and water. The aqueous layer is Washed twice more with ether,the combined ether solutions are washed with sodium bicarbonatesolution, and the latter extract is again extracted with ether. Thecombined ethereal layers are washedonce'with salt solution, dried(MgSO4), and-evaporated. The remaining dioxan is completelyremoved onthe water pump. The residue consistingof the crude ketol, partlysolidifies on being seeded with a specimenof pure-ketol (M; P. 7172'C.).

Ketal acetate IV)'.The crudeketol (58 g.) is dissolved in dry pyridine(300' cc. reagent grade pyridine acetic anhydride. (60 ..cc..reagentgradeyis added. The solution from. which moisture .iS .excluded-by acalcium chloride tube, .is' heated on the; steam 'bathtfor; a fewsmin-.utes, and is thenset-aside overnight. ,Most-of the pyridine. is removedjfromtherred solution;at.the:water,pump, ether is added to the residueand .lh61S0lUtl0I1 is.-washed with water, excess dilutesulfuricacid,,sodiumbicarbonate and finally water. .Eachaqueous :washingfisextracted with ether, and the combined' ether =solutions are driedand'evaporated. .The crude acetate tremainsasadather mobile orange oil.

Bicyclic ketone (V) .The. crudexacetate:(601g) :anil redistilled acetic'anhydride (550- cc.) are heatedwto 14515 0 C. .in a. paraflinbath withstirring under-reflux, with'the exclusion of moisture. CommercialI-zinedust (550 .g..).,is added all at once,,and the.mixturepisstirredvigorously at this. temperature for 8 minutes. The mixture'is'cooledinice with stirring,.tlie zinc is removed by filtration and thoroughlywashed with.ether. The .ether s evaporated on'the steam bath, andtheac'eticanhydride is distilled ofi onthe water. pump. The 'lightyellow residue (ca. g.) containing some solid .is -.diluted.-with ether,and washed with .water, dilute sulfuric acidia'nd again water. Theagueouszlayers are extracted with ether, andth-e combined zethersolutions are washed. twice w th sodium carbonate. solution (each time.for ca. ,5 mins.) and-then with water. The combined aqueouslayers arewashed with. ether, the combined ether extracts are dried (MgSOt) andevaporated. The residueis .distilled roughly into twofractions:

(a) B. P. 68:98 CJOA mm. and (b) B. P. 117-l'3.7 C./.O.4.mm.

Fraction (a) is redistilled slowly through a small -V1greuxcolumn-togive the bicyclicketone. (.V). as a colorless mobile liquid,B. 1. 80-251' C./ 0.8' mm., .n 1.5167. On being seeded atroom'temperature.(-25 C.) it nearly completely .solidifies, M. P. 20-29C..

Hydroxymethylene ketone' Vl ..Commercialsodium methoxide (35 g.) iscovered withdry benzene (175.60.) and redistilled ethyl formate (87.cc.).is ,addedina thin stream to the stirred mixture at room temperature imanitrogen atmosphere. Stirringjs continued at-.room..tem,- perature tor afurther /2 hour, when the mixtureis cooled in ice. The bicyclic ketone.(35 g.) ,in dry-be'nzene 175 cc.) is added dropwise during 45'-minuteswith ice-cooling. More benzene (175 ,cc.) .is added, and stir: ring inmtrogen is continued for a further v.12 hours at room temperature. About30 minutes after ,the .end of the: addition a voluminous yellowgelatinous precipitate separates, which does not change inappearancewhen thexrreaction -wasterminated. Ether and need dilute.sulphuric' aci'dare added',--the aqueous layer' is washed with ether,and the combined-ethereal layers are washed with excess potassiumhydroxide solution. The red-brown alkalineaqueous'layer is washed oncewith ether, aciditied: with dilute hydrochloric acid,.and.extractedtwice w th ether. The latter ether washings are washed once WllhWaI6h,;dr16Cl', and evaporated. The residue contains somez forrnic acid,and is therefore distilled through a smal1-=V1greuxcolumn. This yieldsthe hydroxymethylone ketone V1) as a yellow mobile. liquid, B. P. 8890C./0.015 mm., n 1.5552.

7 More conveniently the hydroxymethylene compound may be isolatedwith:benzene instead of ether. in that case the'formic acidlis...removedwhen distilling. off .the benzene, and the crude undistilledhydroxymethylene -ketonemay bellsed for the next stage.

Ezhyl' vi nyl ,ketone ,adduct (VII)..A solution of freshlydistilledethylvinyl ketone (15.0 .g.) .and distilled hydroxymethylene ketone.(VL) (29.0 g.) are dissolved in.dry redistilled .tert-butanol .(120cc.). The solution .is cooled in ice, the ,air.-is..displaced withnitrogen, and a solution of potassium tert-butoxide, prepared bydissolvmg potassium (600-mg..) :ii1.dry tert-butanol (22.5 cc.-), isadded. Thesolution is .cooled until the butanol just starts tocrystallize. The.air==is-again displaced with nitrogen, and the solutionis--left at .room temperature for 10;hours-. Qn scratching a heavyprecipitate separates; themixture is IQfi-COOlfid, the adductis.filtered and. washed-withcold bizltgazgn ol2 On'being dried, theWhitesparkling plates melt a Tricyclic ketone. (VIII)..-The crystallineethyl vinyl kept over potassium hydroxide for several. days), and g5ketoneadduct-(VIl') (18.9.,g.) is dissolved in redistilled dioxan (760cc.) and the solution is cooled in ice. A cooled solution of potassiumhydroxide (19 g.) in water (760 cc.) is added, and the solution isallowed to stand at room temperature (ca. 30) for 3 hours withoccasional shaking. The initially clear solution becomes turbid after afew minutes and a small upper layer separates. Ether and water areadded, the aqueous layer is washed twice with ether, the combinedorganic extracts are washed with water untll neutral, and are then driedand evaporated. The dioxan is finally removed at the water pump, whenthe res due on being cooled completely solidifies. Crystallization frommethanol yields the tricyclic ketone (VIII) as prisms, M. P. 70.5-72.5C.

Tricyclic ketone glycol (IX ).Osmium tetoxide (32.394 g.) is dissolvedin Na-dried ether (350 cc.) or in benzene and ether 100 cc. benzene, tomake a 27% solutron, plus 250 cc. ether) and cooled. The Os04 solution1s added to a cooled ether solution (730 cc.) of tricyclic ketone (VIII)(29.791 g.; 20 mg. in excess of calculated amount) with swirling. Thesolution is set aside at room temperature in a dark place for to 8 days.The ether solution is decanted through a filter, and the complex isdissolved in methylene dichloride (500 cc.) and shaken mechanically witha solution of mannitol (167 g.) and potassium hvdroxide (47.5 g.) inwater (1250 cc.) for 1 hour or until the methylene chloride layer isvery pale yellow. The methylene chloride layer is separated; the aqueouslayer is saturated with sodium chloride and extracted four times withchloroform. The combined CHaCl2CHCls extracts are washed twice withsaturated sodium chloride solution, dried with anhydrous NazSOa, andconcentrated on the steam bath and in vacuo. The residual gum istriturated with benzene 125 cc.). After cooling somewhat the whitesolids are filtered 01?. They melt at 135-150 C., and give the desiredglycol (IX),

M. P. 152-156 C., after one recrystallization from CHCls-benzene.

Tricyclic isonropylidine ketone (X ).-The tricyclic ketone glycol (IX)(20 g.) is placed in a strong 2-liter Pyrex bottle with anhydrous CuSO t(100 g.) and dry acetone (2000 cc.). The bottle is stoppered securelyand shaken mechanically for 36 hours. The CuSO4 is removed by filtrationthrough sintered glass, and the acetone solution is shaken with a smallamount of anhydrous K2CO3, filtered, and evaporated to dryness using aWater aspirator. The residue, on crystallization from benzenepetroleumether, gives the isopropylidene compound (X), M. P. 95-98 C.

Mono-unsaturated tricyclic isopropylidene ketone (X I ).-The tricyclicisopropylidene ketone (X) (14.727 g.) is stirred in an atmosphere ofhydrogen in the presence of prereduced 2% palladium on strontiumcarbonate catalyst (7.3 g.) in 100 cc. Na-dried benzene. In 3 hours 25minutes, 1224 cc. hydrogen has been absorbed by which time theabsorption of hydrogen has become drastically slower and the reductionis stopped. The catalyst is filtered off through a sintered glassfunnel. and washed with reagent grade benzene, and most of the benzeneis removed in vacuo. The residual solution is diluted with petroleumether and the mono-unsaturated tricyclic isopro vlidene ketone (XI)separates as a fine White powder, M. P. 153156 C.

Hvdroxvmethylene mono-unsaturated tricyclic isopronvlidene ketone (XII).n an atmosphere of nitrogen. freshly prepared sodium metho ide (13.1 g.)is covered with drv benzene (175 cc.) and KvCos-dried and distilled ehvl formate (33 cc.) is added to the stirred mixture in a thin stream.The mixture is stirred at room temperature for 30 minutes. and asolution of the mono-unsaturated tri vclic isopr vlidene ketone (24 g.)in dry benzene (150 cc.) is added. Stirrin at room temperature iscontinued for about 1 hour or until the mixture has solidified to aelatinous mass. After standin under nitrogen overni ht. hos hate buffersoluti n (1 06 cc.; 156 cc. 0.7 M KH-PO4 plus 1250 cc. 0.7 M Na2HPO4) isadded with stirring, and the layers are separated. The pH of the aqueouslaver is adjusted to pH 8 by adding a few cc. of the KH?PO4 solution, ifnecessary. The solution is extracted with ether 4 times, the combinedorganic layers are dried with Na2SO4 and concentrated to dryness on thesteam bath and in vacuo. The crude hydroxymethylene compound (XII)solidifies when all the solvent is removed.

Methylanilino derivative (XIII ).The crude hydroxy- 8 methanol (275 cc.)and methylaniline (57 cc.). After standing overnight the yellowcrystalline methylanilino compound (XIII) is filtered off and washedwith petroleum ether until the odor of methyl aniline can not bedetected. It melts at 218222.5 C.

Cyanoethyl derivatives (XlVa and XIVb).-The methylanilino derivative(XIII) (30.2 g.) is dissolved by warming in a mixture of dry benzene(500 cc.) and dry t-butanol (1000 cc.). Acrylonitrile (13.2 g.) andTriton B (48.5 cc. of a 3.5% solution in t-butanol+3.5 cc. water) areadded. The air is displaced by nitrogen and the reaction mixture is leftat 50 C. for 45 hours. The solvents are removed in vacuo and the darkred residue is eluted several times with ether (ca. 400 cc.) to separateinsoluble acrylonitrile polymer. Evaporation of the ether leaves thestereoisomeric cyanoethyl derivatives (XlVa and XIVb) as an orange gum.

Carboxyethyl derivatives (X Va and X Vb).-The cyanoethyl derivatives(XIVa and XIVb) are preferably not separated but are converted to thecorresponding carboxyethyl derivatives by vigorous basic hydrolysis. Themixture of (XIVa and XIVb) (ca. 35 g.) is refluxed for 7 hours undernitrogen with potassium hydroxide (40 g.) and water (250 cc.).

Extraction with ether afiords a small quantity of monounsaturatedtricyclic isopropylidene ketone XI. Acidification of the aqueous layerwith cold dilute (1: 10) hydrochloric acid in the presence of etherfollowed by two ether extractions, drying and thorough removal ofvolatile materials gives a crude mixture of the stereoisomeric acids(XVa and XVb). Repeated trituration with ether causes the precipitationof isomer (XVa), M. P. 148- 150 C. (labile form) and 173 C. (stablevform). Crude isomer (XVb) is left as an amber gum on evaporation of theether.

Enol lactone (XVI).Crude isomer (XVb) (10.7 g.) and distilled aceticanhydride (80 cc.) are refluxed for 2 hours under nitrogen. Sodiumacetate (0.1 g.) is added and refluxing is continued for 2 hours more.Most of the acetic anhydride is removed in vacuo. Ether is added and theether solution is washed with dilute sodium carbonate solution andwater. Evaporation of the dried ether extract leaves a residue whichpartially crystallizes on addition of ether, to give crude enol lactone(XVI), M. P. 185210 C. Further crops of less pure (XVI) may be obtained.The highest M. P. of this compound has been 240 C. (dec.), but materialmelting above C. is satisfactory for further reaction.

D-homosteroid (XVIl).-The enol lactone (XVI) (2.18 g.), M. P. 185-210C., is dissolved in dry benzene (40 cc.) and dry ether 40 cc.) undernitrogen. The mixture is cooled to 18 C. and a solution ofmethylmagnesium bromide in dry ether (21.3 cc.; 0.285 N) is addeddropwise with vigorous stirring over 2-3 hours. Dilute hydrochloric acid(60 cc., 1:10) is added rapidly with stirring. The layers are separatedand the aqueous layer washed with ether. The combined ether layers arewashed with a little cold water, dried and the solvent removed. Thesolid residue is refluxed for 2 hours under nitrogen with methanol cc.),water (20 cc.) and sodium hydroxide (1.95 g.). Saturated salt solutionis added, and the product is extracted with ether. The dried extract on.evaporation gives the D-homosteroid (XVII), which on crystallizationfrom ethanol or benzene-ligroin has M. P. 199202 C.

.Dialdehvde (XV!H).-The D-homosteroid (XVII) (2.10 g.) is dissolved inpure dioxan (175 cc.), and periodic acid (4.1 g) in Water (28 cc.) isadded. The homogeneous solution is allowed to stand at room temperaturein a nitrogen atmosphere for 15 hours; most of the dioxan is thenremoved in vacuo, water is added to the residue, and the product isextracted with ether. The dried extract is evaporated to yield the crudedialdehyde as a crystalline residue, which on crystallization from etherhas M. P. 128132 C.

Steroid (XiXa).Heating the dialdehyde (XVIH) in solution recloses ring Dto give the 17-aldehyde steroid (XIXa). The dialdehyde (XVIII) (1.87 g.)is dissolved in pure dioxane (100 cc.) containing a trace ofhydraquinone. Pure water (64 cc.) is added, and the solution is heatedin sealed glass tubes in a nitrogen atmosphere for 7 /2 hours at 145 C.Ether is then added, the solution is washed with sodium bicarbonatesolution and water, and is dried and evaporated. Ad-

dition of methanol causes the precipitation of the steroid (XIXa), M. P.165-470 C. The mother liquors are sublimed at 160"/10" mm., and thesublimate with methanol gives a further crop of (XIXa). The combinedcrops on crystallization from methanol give pure (XIXa), M. P. 171173 C.The mother liquors, after the second crop of the steroid has beenremoved, give further crops of crystalline material. Recrystallizationof these from aqueous methanol gives impure isomer (XIXb), M. P. 145-150C.

The dialdehyde (XVIII) may also be converted into the tetracyclic17-aldehyde (XlXa) in good yield by heating a solution in benzene at 60C. in the presence of piperidine acetate for about an hour.

Comparison of derivatives of the 17-aldehyde with similar derivatives ofthe naturally occurring steroid hormones of the adrenal cortex, such asKendalls compound E, shows that the 17-aldehyde is identical in stericconfiguration with the natural steroid hormones. A method for theconversion of the tetracyclic 17-aldehyde (XIXa) into cortisone isdescribed in Journal of the American Chemical Society, vol. 73 (1951),at page 4057, and methods for the conversion of the compound intoprogesterone testosterone and other steroids are described in Journal ofthe American Chemical Society, vol. 73 (1951), at pages 3547 and 3548.

This application is a continuation-in-part of my application Serial No.220,977 filed April 13, 1951.

Subject matter disclosed in this application is also claimed in myapplications Serial Nos. 269,328 and 269,329.

I claim:

1. The method which comprises heating a solution of 1,2bis(aldehydomethyl) 2,13 dimethyl 7 keto-1,2,3,5,6,7,9,10,11,13-decahydrophenanthrene in an organic solvent andrecovering the aldehydo-steroids thereby produced.

2. Aldehyde-steroids of the group consisting of CEO i ii .Q

hit. .133

3. A9,(1l),l6-bisdehydro 21 norprogesterone of the formula and 4. Themethod which comprises heating a solution of 1,2 bis(aldehydomethyl)2,13 dimethyl 7 ketol,2,3,5,6,7,9,10,11,13 decahydrophenanthrene in anaromatic hydrocarbon solvent in the presence of a salt of inorganicnitrogen base and a carboxylic acid and recovering the aldehydo-steroidsthereby produced.

5. The method which comprises heating a solution of 1,2bis(aldehydornethyl) 2,13 dimethyl 7 keto- 1,2,3,5,6,7,9,10,11,13decahydrophenanthrene in an aromatic hydrocarbon solvent in the presenceof piperidine acetate and recovering the aldehyde-steroids therebyprouce References Cited in the file of this patent FOREIGN PATENTS516,542 Great Britain Jan. 4, 1940

1. THE METHOD WHICH COMPRISES HEATING A SOLUTION OF 1,2 -BIS(ALDEHYDOMETHYL) - 2,13 - DIMETHYL - 7-KETO1,2,3,5,6,7,9,10,11,13-DECAHYDROPHENANTHRENE IN AN ORGANIC SOLVENTAND RECOVERING THE ALDEHYDO-STEROIDS THEREBY PRODUCED.